tbuckley/cabot-search huggingface dataset:
SARC037: Results of phase I study of trabectedin given as a 1-hour (h) infusion in combination with low dose irinotecan in relapsed/refractory Ewing sarcoma (ES).
Authors: Patrick Grohar, Karla V. Ballman, Rachel Heise, John Glod, Mary Frances Wedekind, Leo Mascarenhas, Jenna Marie Gedminas, Steven G. DuBois, Robert G. Maki, Brian D. Crompton, Masanori Hayashi, Cody J. Peer, William Douglas Figg, Maria Liza Lindenberg, Esther Mena Gonzalez, Rochelle Bagatell, Theodore Willis Laetsch, Brigitte C. Widemann, Denise K. Reinke, Rashmi Chugh
Journal: Journal of Clinical Oncology (2023)

11519 Background: Recurrent ES carries a poor prognosis, and systemic therapies have limited efficacy. Preclinical models suggested that trabectedin (T) could achieve serum concentrations high enough to suppress the dominant oncogene of ES (i.e. EWS::FLI1 transcription factor), and that this effect is sustained by subsequent administration of low dose irinotecan (I). We conducted a phase I study of T+I in patients (pts) with ES. Methods: This multicenter dose escalation study employed a standard 3+3 design. T was given as a 1-h infusion on day (D)1 with low dose I intravenously on D2 and 4 of a 21D cycle. Dose limiting toxicities (DLTs) were evaluated in cycle one. Eligibility required confirmed EWS::FLI1 fusion transcript, age ≥10 years, ECOG performance status ≤2, adequate organ function and willing to have a research biopsy if safely accessible. Primary objectives were to determine the recommended dose (RD) and safety of T+I. Secondary objectives comprised efficacy of T+I and avidity of ES for 3'-Deoxy-3'- 18 F Fluorothymidine ( 18 F-FLT) PET. Results: 20 pts enrolled from 1/2021-12/2022 across 5 sites, 5F/15M, median age 18 years (range 10-59). Pts had received a median of 4 (range 2-9) prior therapy lines including irinotecan in 60% of pts. Grade (G) 3/4 treatment-emergent adverse events (TEAEs) occurring in ≥10% of pts were: elevated ALT/AST, elevated creatinine phosphokinase, febrile neutropenia, anemia, lymphopenia, neutropenia, and thrombocytopenia. There were 2 G5 respiratory TEAEs. 18 F-FLT PET scans were obtained in 5 pts. ES tumors were 18 F-FLT PET avid. Dose level (DL)2 was the RD. At DL 2 and above, there were 4 PRs, 6 SD in 14 evaluable pts (Table). Conclusions: T+I can be safely administered to heavily pretreated pts with ES, demonstrating activity at the RD with 3 PRs (n=5 evaluable). The 18 F-FLT PET may be useful to understand patterns of disease progression in ES. Correlative studies will be critical to understanding the mechanism of drug activity. Given the clinical benefit seen with T+I at RD, a phase II portion in pts with ES ≥6 years old is actively accruing. Clinical trial information: NCT04067115 . [Table: see text]
Technology-enhanced acceleration of germline evaluation for therapy (TARGET): Results of a randomized controlled trial of a pretest patient-driven webtool vs. genetic counseling for prostate cancer germline testing.
Authors: Veda N. Giri, Scott W. Keith, Heather H. Cheng, Amy Leader, Laura Gross, Tatiana Sanchez Nolasco, Nataliya Byrne, Rebecca Hartman, Lauren Brown, Christopher Michael Pieczonka, Leonard G. Gomella, William Kevin Kelly, Costas D. Lallas, Nathan Handley, Patrick Johnston Mille, James Ryan Mark, Gordon Andrew Brown, Sameer Chopra, Alexandra McClellan, Stacy Loeb
Journal: Journal of Clinical Oncology (2023)

10598 Background: Germline genetic testing is important for prostate cancer management, clinical trial eligibility and hereditary cancer risk assessment. Despite this, genetic testing is underutilized and there is a shortage of genetic counselors. To address these gaps, we designed a webtool to provide patient-driven genetic education and conducted a randomized non-inferiority trial to compare it with traditional pre-test genetic counseling. Methods: TARGET is a multi-center randomized controlled trial comparing standard pre-test genetic counseling versus web-based genetic education (intervention) (NCT04447703). The study protocol was previously published (PMID 35710085). Briefly, patients with prostate cancer who met criteria for germline testing (based on tumor features, ancestry or family history) were randomized to pre-test genetic education through genetic counseling vs a 9-module webtool created by the study team and Prostate Cancer Foundation. The primary endpoint was non-inferiority in reducing decisional conflict between the webtool and genetic counseling by a margin of 4 (set in advance) on the validated Decision Conflict Scale. Analysis of covariance was used to compare decisional conflict between groups. All participants opting for testing received a 51-gene Invitae panel, with results delivered to the patient and their provider. Results: 346 patients with prostate cancer with a mean age of 63.7 years were randomized to genetic counseling (n=174) or web-based genetic education (n=172). Compared to baseline, there were reductions in decisional conflict in both arms following pre-test genetic education (Table). Adjusting for study site and baseline decisional conflict, the test of non-inferiority in reducing decisional conflict between arms was statistically significant (difference = -0.04, 95% CI: -∞ to 1.95, p&lt;0.001). Overall 265 (76.6%) participants underwent genetic testing, including 146 (83.9%) in the genetic counseling and 119 (69.2%) in webtool arm, with the following results: negative (49.4%), variant of uncertain significance (35.5%) and pathogenic variant (15.1%). Conclusions: Delivery of pre-test genetic education through a webtool was non-inferior to genetic counseling in reducing decisional conflict. These results support a new standard of care for the use of patient-driven digital webtools for expanding access to pretest genetic education and informed decision-making for prostate cancer genetic testing. Clinical trial information: NCT04447703 . [Table: see text]
Impact of breast cancer on employment in Mexico.
Authors: Cynthia Villarreal-Garza, David G. Gonzalez-Sanchez, Arantxa Ramirez, Daniela Vazquez Juarez, Alejandra Platas, Ana Laura Platas
Journal: Journal of Clinical Oncology (2023)

e24219 Background: Women constitute 40% of the workforce in Mexico and are essential contributors to the household and national income. Understanding how BC impacts an individual’s work-life and how the workplace supports patients’ journeys is important to understand the economic burden of this disease. This study focuses on the changes in the employment status of Mexican BC patients after their initial treatment. Methods: An online survey was created and distributed throughout Médicos Investigadores en la Lucha Contra el Cáncer, a BC NGO, social media networks from July to November 2022. Patients with BC who had completed initial treatment and lived in Mexico were invited to participate. The survey consists of multiple-choice questions and the opportunity to explain certain responses. Results were analyzed and visualized using Excel and RAWGraphs. Results: A total of 73 participants completed the survey. The average age (range) of participants was 46 years old (26-66) and 50.7% reported living as a couple. 84% of patients had completed high school or higher education. Most participants had stage 2 (34%) or stage 3 disease (33%). Table 1 describes the employment status of the other 73 participants before, during, and after initiating treatment. 53% considered having the support of their colleagues and employer during their initial treatment. The rest considered that their work environment was indifferent (21%), offered no support (14%), or decided not to disclose their diagnosis (12%). Additionally, some patients commented about workplace discrimination because of their disease: “Customers wouldn’t purchase clothes because my lack of a breast disgusted them” (after a radical mastectomy) and “I was forced to quit because “it was better for me” and they were afraid I would infect them.” Financial necessity (45%) and a return to normalcy (33%) were the main motivators to return to work, and 14% did not wish to continue working at the time of the survey. Conclusions: After their initial treatment, the majority of patients in this study underwent changes in employment status or stop working altogether. A considerable portion of the participants did not feel supported by their workplace and some even faced discrimination due to their disease. Future studies need to be conducted to understand the physical and psychological aspects, and the employer and societal factors that limit cancer survivors’ successful return to work in Mexico. Advocacy and reform must be undertaken to decrease workplace discrimination and balance work-life and breast cancer care. [Table: see text]
Unveiling inequities in palliative care and clinical trial participation among patients with metastatic breast cancer in the state of Florida.
Authors: Oluwadamilola Temilade Oladeru, Young-Rock Hong, Fantine Giap, Julie Ann Bradley
Journal: Journal of Clinical Oncology (2023)

12120 Background: Persistent inequities in the care for patients with metastatic breast cancer (mBC) were recognized by ASCO and, in partnership with Pfizer, awarded our team a grant to understand and address them in people of color. Florida has a higher age-adjusted percentage of breast cancer in females and a higher mortality rate in those under the age of 65 compared to the United States. The racial disparity in mortality is further magnified among female patients with mBC. Therefore, we sought to characterize the prevalence and trends of palliative care utilization and clinical trial participation (CTP) among Floridians with mBC and quantify the associated factors. Methods: Using the OneFlorida+ Data Trust, a repository of patient-level electronic health records of ~17 million Floridians seen in public and private health care systems, including those enrolled in Medicaid, we obtained demographics of mBC patients, including sex, age, race, and ethnicity, insurance type, zip-code based socioeconomic status, Charlson comorbidity index (CCI) and rural/urban residence. CPT codes were obtained for palliative care services between the date of mBC diagnosis and death, including pain management, psychology, psychiatry, nutrition, and advanced care planning. Our analysis included the Cochran-Armitage trend test and bivariate analysis to correlate patient characteristics to palliative care receipt and CTP. Results: In Florida, 25,225 individuals (1.5% men and 98.5% women) were diagnosed with mBC between 2012 and 2021; 49.3% were under age 60. 19.5% of this cohort received palliative care at a median time of 10.1 months (IQR 2.1 – 27.1) from the initial diagnosis of mBC. The median survival was 13.6 months (IQR 3.4 – 31.6). On multivariable analysis, significant variables (p &lt; 0.001) associated with increased palliative care utilization were Non-Hispanic Black, self-pay/uninsured and Medicaid insured, and a CCI of 5+. Only 3% of the study cohort had advanced care planning. There was a declining trend in CTP among patients with mBC, from 13.9% in 2012 to 7.9% in 2021. Among those participating in clinical trials, 80.2% did not receive palliative care. Variables associated with higher CTP (p &lt; 0.001) were younger age (18-49), Asian and Hispanic race/ethnicity, the highest quartile of median household income and education level, private insurance, metropolitan residence, and CCI of 0. Further, there was a trend towards more prolonged survival among those enrolled in clinical trials. Conclusions: This robust statewide assessment highlights that less than 20% of patients with mBC receive palliative care, and its receipt is exclusive of CTP. We identified significant racial and socioeconomic disparities in CTP. Educational interventions with palliative care trained navigators, partnerships with providers on palliative care benefits, and state policy support are needed.
Beyond the binary: Analysis of esophageal cancer hospitalizations in the transgender population, a national inpatient sample study.
Authors: Lekha Yadukumar, Yuvaraj Singh, Neethi Dasu, Yaser Khalid, Maya Gogtay
Journal: Journal of Clinical Oncology (2023)

e18888 Background: Transgenders are individuals with a gender identity that differs from their sex at the time of birth. Over &gt; 1.6 million adults identify themselves as transgender in the US, of which 39% are women and 36% are men. While gender differences in cancer prevalence have been well established between men and women, very few studies evaluate the prevalence of cancer in patients who identify as transgender people. We aimed to evaluate the trends of esophageal cancer admission hospitalizations in the transgender population compared to the general population. Methods: This was a retrospective analysis of the data obtained from the Nationwide Inpatient Sample database. Data were sampled from 2015 to 2020 utilizing the ICD-10 codes of esophageal cancer and patients( &gt; 18 years) who identified as transgender. The primary outcome was in-hospital mortality. Secondary outcomes were the length of stay (LOS) and total costs in the hospital, respectively. A multivariate logistic regression analysis was used to estimate the odds ratio. Results: A total of 212,425 patients with esophageal cancer were admitted between 2015- 2020, of which 97,950 were transgender. The mean age was 33 vs. 34 years in the general population. Both groups were predominantly Caucasian (65% vs. 68%), followed by African Americans (15.2% vs. 5.2%). Median household income (MHI) in transgender people was commonly in the lower quartile (27.8%). In cisgender patients, 37% had a MHI in the 26 th -50 th followed by 26% in the 76 th -100 th percentile. Inpatient mortality in transgender patients with esophageal cancer was OR = 5.1[1.8-8.3] (p &lt; 0.05). The average LOS was higher in the transgender population by 2.15 days [1.1-3.1](p &lt; 0.05). Increased LOS in teaching hospitals by 1.3 days [1.08- 1.59] (p &lt; 0.001) and larger hospitals by 1.4 days [0.51- 2.28] (p &lt; 0.001) was observed. The total cost of admission was significantly different in teaching hospitals ($27,774, p &lt; 0.001). Conclusions: We found a significant difference between the inpatient outcomes of transgender and the general population. Despite the markedly low representation of transgender people in the national cancer registries, they experienced an increased mean length of stay and mortality compared to cisgenders with esophageal cancer. Further investigation is required to determine the cause of disparity in healthcare utilization amongst the gender-diverse population. [Table: see text]
The association between body mass index and distribution intensity of tumor treating fields (TTFields) in the lungs.
Authors: Carly Mooney, Ariel Naveh, Nadav Shapira, Brian Berger
Journal: Journal of Clinical Oncology (2023)

e20559 Background: Tumor Treating Fields (TTFields) therapy is a first-in-class locoregional and noninvasive cancer treatment modality. TTFields are electric fields that disrupt processes necessary for cancer cell viability and tumor progression. A portable medical device generates TTFields, which are delivered noninvasively to the tumor area via 2 pairs of transducer arrays placed on the skin. TTFields therapy is currently approved for recurrent and newly diagnosed glioblastoma and pleural mesothelioma, with studies underway in other solid tumor types, including non-small cell lung cancer (NSCLC). Preclinical studies have shown that the effectiveness of TTFields depends on several factors, including field intensity. Given that 1 in 3 adults is overweight or obese, it is relevant to determine the effect of body mass index (BMI) on TTFields intensity to the lungs. Simulation-based methods were utilized, with the hypothesis that TTFields could be delivered to regions of interest (ROI) at therapeutic field intensities of &gt; 1 V/cm, irrespective of BMI. Methods: Female computer phantom models with BMIs of 22 (healthy), 26 (overweight), and 30 (obese) were used to simulate TTFields intensity using small (13 disk) and large (20 disk) arrays placed on the thoracic region. The distribution of TTFields in each model was then determined using a computer-generated electric field intensity map. Field intensity values across the entire lungs were analyzed and compared. Results: When TTFields were delivered with large arrays, field intensities were clinically meaningful ( &gt; 1 V/cm) in all lobes of the lungs for all BMI models. When TTFields were delivered with small arrays, meaningful levels of field intensity were achieved in all lung lobes, except for the BMI 30 model, where field intensities were slightly lower than 1 V/cm in the right middle lobe. Conclusions: These results show that TTFields can be delivered at therapeutic field intensities in patients with a BMI up to 30, providing the appropriate TTFields array size is used. Results from this simulation-based study support current clinical studies of TTFields therapy in lung cancer, (LUNAR, NCT02973789) and underscore the importance of appropriate array size selection. Additionally, these results may provide guidance for using TTFields therapy to treat a broad population of patients with lung tumors.
Clinical and molecular characteristics of multiple primaries identified by whole-exome sequencing-based genetic divergence in non-small-cell lung cancer.
Authors: Ning Liu, Yongsheng Wang, Xue Li, Lili Jiang, Weiya Wang, Qizhi Ma, Jie Tang, Daxing Zhu, Jiandong Mei, Benxia Zhang, Pei Shu, Yue Chen, Diyuan Qin, Fuchun Guo
Journal: Journal of Clinical Oncology (2023)

e20558 Background: With the recommendation of high-resolution chest computed tomography scan in lung cancer screening, multiple primary lung cancers (MPLC) is gaining more attention. Identifying MPLC from intrapulmonary metastases (IPM) is crucial to the clinical management. The current guidelines for the identification are always based on expert consensus rather than clinical evidence. We aim to develop a reliable identification method and further figure out the clinical and genetic features of MPLC. Methods: We retrospectively screened 305 lung lesions from 131 patients who underwent radical resection for multiple lung carcinomas. To minimize the effect of therapeutic intervention on prognostic outcomes, patients with each single tumor size smaller than 4cm, free of nodal or systemic metastases, and had high-quality whole-exon sequencing (WES) data were included. We selected 11 patients with confirmed intrapulmonary metastases for training. All patients’ follow-up information was collected until disease recurrence or metastases. A WES genetic divergence method for identifying MPLC from IPM was developed. The disease-free survival (DFS) was used as a validation tool for identification reliability. Results: A total of 61 eligible multi-lesion patients with 128 resected non-small cell lung cancer (NSCLC) lesions were finally analyzed. Based on WES genetic divergence identification, 51 MPLC patients were identified, whose DFS was significantly prolonged (HR, 0.27; 95% CI, 0.08 to 0.91; P = 0.02), while other recommended methods for identifying MPLC patients failed to show a DFS advantage. Among MPLC patients, 43.1% (22/51) had a first-degree relatives cancer family history, of whom 54.5% (12/22) had a lung cancer family history. EGFR was still the most common mutation gene (72.5%, 37/51); however, TP53 mutations was less frequent in MPLC (21% vs. 48%, P &lt; 0.05), and tumor mutation burden (TMB) was lower (median, 0.73 muts/Mb vs. 1.15 muts/Mb, P &lt; 0.01). Notably, despite the lack of shared alterations, unique germline variants in cancer-predisposing genes, particularly nonsynonymous SNV in solute carrier gene (SLC) family, were observed in most MPLC patients, rarely overlapping with IPM patients. Conclusions: WES-based genetic divergence clearly distinguishes independent primary tumors from IPM in NSCLC patients. MPLC patients represent a unique population which deserves further study.
Association of Medicaid expansion with timely receipt of treatment and survival among patients with HER2-enriched breast cancer.
Authors: Kewei Sylvia Shi, Xu Ji, Changchuan Jiang, Kathryn Jean Ruddy, Sharon M. Castellino, Robin Yabroff, Xuesong Han
Journal: Journal of Clinical Oncology (2023)

6539 Background: HER2-enriched breast cancer (estrogen and progesterone receptors negative and HER2-positive) has no worse prognosis than other breast cancers if it is treated with HER2-targeted therapy. Medicaid expansion under the Affordable Care Act (ACA) has been shown to be associated with improved access to care and outcomes for many cancers, but its impact on care for HER2-enriched breast cancer is unknown. To fill this gap, we examined the association of Medicaid expansion with receipt of guideline-concordant treatment, time to treatment, and survival among newly diagnosed nonelderly women with HER2-enriched breast cancer. Methods: Women aged 18-62 years newly diagnosed with HER2-enriched breast cancer between 2010 and 2018 were identified from the National Cancer Database. Our primary outcomes included receipt of stage-based guideline-concordant treatment, initiation of treatment &lt;60 days, and stage-specific 2-year overall survival. A difference-in-differences (DD) approach compared outcome changes following the expansion in Medicaid expansion vs. non-expansion states. A linear probability model estimated treatment outcome, and a flexible parametric survival model evaluated survival. All models were clustered at the state level and adjusted for age group, race/ethnicity, rurality of residence, zip code-level income, comorbidity, and diagnosis year. Results: A total of 31,354 patients with HER2-enriched breast cancer were included, including 19,255 in expansion states and 12,099 in non-expansion states. Compared to patients in expansion states, patients in non-expansion states were more likely to be racial/ethnic minorities, uninsured, and diagnosed at late-stage. Medicaid expansion was not significantly associated with changes in receipt of surgery for stage I-III disease but was associated with an increase of 4.42 percentage points (ppt, 95% CI: 0.09, 8.74) in receipt of chemotherapy/targeted therapy for stage IV disease, with an increase from 90.4% pre-expansion to 92.8% post-expansion in expansion states and a decrease from 93.7% to 91.9% in non-expansion states. Medicaid expansion was also significantly associated with a 2.41 ppt increase in initiating guideline-concordant treatment within 60 days (95% CI: 0.66, 4.17; 83.5% to 82.5% in expansion states vs. 86.6% to 83.7% in non-expansion states), and a 1.18 ppt increase in two-year survival rate (95% CI: 0.03, 2.33; 94.0% to 94.9% in expansion states vs. 94.3% to 94.1% in non-expansion states). The increase in two-year survival associated with Medicaid expansion was most prominent for stage III patients (DD=3.63 ppt; 95% CI: 0.64, 6.62). Conclusions: Medicaid expansion was associated with increased receipt of timely treatment and improved 2-year survival among nonelderly women newly diagnosed with HER2-enriched breast cancer.